Evaluation of Clinical Efficacy and Immunologic Response After IL-2 Therapy in HCV-related Vasculitis Patients

Cryoglobulinemia Vasculitis Clinical Trial

Official title:

ANRS HC 21 VASCU IL-2, Evaluation of the Cellular Immune Response, Clinical Efficacy and Tolerance After IL-2 Therapy in HCV-related Vasculitis Patients, Resistant to Conventional Therapy.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00574652
• Other study ID #: 2006-004039-31
• Secondary ID: ANRS HC 21 Vascu
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 14, 2007
• Last updated: January 23, 2013
• Start date: March 2008
• Est. completion date: September 2010

Study information

• Verified date: January 2008
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

A systemic Vasculitis is found in 5 to 10% of HCV infected patients with mixed cryoglobulinemia (MC). It mainly involves the skin, peripheral nerve and the kidney and may be life threatening. Twenty to 30% of HCV-MC Vasculitis patients are resistant to conventional therapy (i.e. antiviral therapy and/or immunosuppressors) and still have an active disease. Thus, new therapeutic approaches are necessary in such patients. We recently described a regulatory T cell (Treg) deficiency in HCV-related Vasculitis patients. Immunomodulatory effects of interleukin-2 (IL-2) are well established, notably the preferential expansion of Treg able to suppress inflammatory responses mediated by CD4+ and CD8+ T cells.

Description:

A systemic Vasculitis is found in 5 to 10% of HCV infected patients with mixed cryoglobulinemia (MC). It mainly involves the skin, peripheral nerve and the kidney and may be life threatening (15% of death). Twenty to 30% of HCV-MC Vasculitis patients are resistant to conventional therapy (i.e. antiviral therapy and/or immunosuppressors) and still have an active disease. An antiviral therapy with Peg-interféron is generally prescribed to control Vasculitis lesions and to slow down the hepatic fibrosis progression. Thus, new therapeutic approaches are necessary in such patients. We recently described a CD4+ CD25+ regulatory T cell (Treg) deficiency in HCV-related Vasculitis patients. Immunomodulatory effects of interleukin-2 (IL-2) are well established, notably the preferential expansion of Treg able to suppress inflammatory responses mediated by CD4+ and CD8+ T cells.

Objective : To evaluate the cellular immune response after IL-2 therapy in HCV-MC Vasculitis patients, resistant to conventional therapy.

Methods : This is an open prospective phase I/II trial. Four cycle of subcutaneous IL-2 therapy (3 millions IU/day from day 1 to 5 every 21 days will be carried out at W1, W3, W6, and W9). The first cure will be carried out with half-dose of IL-2 (1.5 millions IU/day) in the hospital. If the tolerance is satisfactory, the later cures will be done ambulatory. All patients will be followed after IL-2 therapy (S11 to S37).

End points :

1. Clinical tolerance: Absence of Vasculitis flare during and after IL-2 therapy.

2. Immunologic follow-up of Treg and of HCV cellular immune response before, during and after IL-2 therapy.

3. Clinical efficacy: follow-up of clinical manifestations of HCV-MC Vasculitis during and after IL-2 therapy.

Schedule : Duration of patients' inclusion period is estimated 18 months. Duration of therapy and follow-up is estimated 9 months. Analysis of data will last 7 months. Overall duration: 34 months

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: September 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. HCV+ patients with cryoglobulinemia Vasculitis

2. resistant to conventional therapy (i.e. antiviral therapy and/or immunosuppressors).

3. Vasculitis is defined according to international criteria: chronic HCV infection (HCV RNA+),

4. serum cryoglobulin superior or equal to 0.05g/l in at least two determinations,

5. presence of the triad purpura-arthralgia-asthenia and/or biopsy proven Vasculitis (kidney, nerve or skin).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cryoglobulinemia
• Cryoglobulinemia Vasculitis
• Vasculitis

Intervention

Drug:
• Proleukin
3 millions IU/day from day 1 to 5 every 21 days will be carried out at W1, W3, W6, and W9)

Locations

Country	Name	City	State
France	Hôpital de la Pitié	Paris

Sponsors (1)

Lead Sponsor	Collaborator
French National Agency for Research on AIDS and Viral Hepatitis

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunologic follow-up of Treg and of HCV cellular immune response before, during and after IL-2 therapy		9 months	Yes
Secondary	Clinical tolerance: Absence of Vasculitis flare during and after IL-2 therapy		9 months	No
Secondary	Clinical efficacy: follow-up of clinical manifestations of HCV-MC		9 months	No